Immunoglobulins (antibodies) in adult humans are categorized into five different isotypes: IgA, IgD, IgE, IgG, and IgM. The isotypes vary in size and sequence. On average, each immunoglobulin has a molecular weight of about 150 kDa. It is well known that each immunoglobulin comprises two heavy chains (H) and two light chains (L), which are arranged to form a Y-shaped molecule. The Y-shape can be conceptually divided into the Fab region, which represents the top portion of the Y-shaped molecule, and the Fc region, which represents the bottom portion of the Y-shaped molecule.
The heavy chains in IgG, IgA, and IgD each have a variable domain (VH) at one end followed by three constant domains: CH1, CH2, and CH3. The CH1 and CH2 regions are joined by a distinct hinge region. A CH2 domain may or may not include the hinge region. The heavy chains in IgM and IgE each have a variable domain (VH) at one end followed by four constant domains: CH1, CH2, CH3, and CH4. Sequences of the variable domains vary, but the constant domains are generally conserved among all antibodies in the same isotype.
The Fab region of immunoglobulins contains the variable (V) domain and the CH1 domain; the Fc region of immunoglobulins contains the hinge region and the remaining constant domains, either CH2 and CH3 in IgG, IgA, and IgD, or CH2, CH3, and CH4 in IgM and IgE.
Target antigen specificity of the immunoglobulins is conferred by the paratope in the Fab region. Effector functions (e.g., complement activation, interaction with Fc receptors such as pro-inflammatory Fcγ receptors, binding to various immune cells such as phagocytes, lymphocytes, platelets, mast cells, and the like) of the immunoglobulins are conferred by the Fc region. The Fc region is also important for maintaining serum half-life. Serum half-life of an immunoglobulin is mediated by the binding of the Fc region to the neonatal receptor FcRn. The alpha domain is the portion of FcRn that interacts with the CH2 domain (and possibly CH3 domain) of IgG, and possibly IgA, and IgD or with the CH3 domain (and possibly CH4 domain) of IgM and IgE.
The CH2 domain (or the equivalent CH3 domain of IgM or IgE) also has binding sites for complement. The CH2/CH3 domain's retention of functional characteristics of the antibody from which it is derived (e.g., interaction with Fcγ receptors, binding sites for complement, solubility, stability/half-life, etc.) is discussed in Dimitrov (2009) mAbs 1:1-3 and Dimitrov (2009) mAbs 1:26-28. Prabakaran et al. (2008, Acta Crystallogr D Biol Crystallogr 64:1062-1067) compared the structure of a CH2 IgG domain lacking N-linked glycosylation at Asn297 to the structure of a wild type CH2 IgG domain and found the two CH2 domains to have extremely similar structures.